Summary of Work: Prostate diseases are a major problem for aging men. Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths in U.S. men. Furthermore, benign prostate hypertrophy (BPH) affects most men by age 80. The Baltimore Longitudinal Study of Aging (BLSA)is defining anatomic and physiologic characteristics that distinguish normal prostate growth with age and the development of prostate disease; identifying hormonal changes important in the diseases; and characterizing markers(serum and genetic) that could identify high risk groups, and increasing knowledge regarding the development and progression of prostate disease, and lead to methods of disease prevention. The BLSA prostate study pioneered the use of prostate specific antigen (PSA) velocity to improve the specificity of PSA. testing. Less than 5% of men without prostate cancer have a rate of change in PSA exceeding 0.75ng/ml per year; while 70% of men with cancer have a rate of change in PSA that exceeds 0.75ng/ml per year. These data have now been confirmed in large prospective screening trials. This year the BLSA reported a study of free PSA levels using frozen sera from men with and without prostate cancer. Free PSA levels were significantly lower in cancer cases 10 years before diagnosis; while total PSA levels were significantly different 4 years before diagnosis. Moreover, the ratio of free to total PSA was lower in men with clinically defined aggressive tumors than in those with nonaggressive tumors. These findings could have important implications regarding early detection of prostate cancer. A genetic study of four genes that may contribute to prostate cancer was initiated during the year. BLSA data were combined with those treated surgically for prostate cancer to evaluate PSA testing intervals that maintain the detection of curable cancer and reduce unnecessary testing. In cases where no cancer was suspected based on digital rectal examination, a PSA level of 4-5 ng/ml is acceptable for maintaining the detection of curable prostate cancer and a 2 year interval is not likely to miss a curable prostate cancer when the initial PSA level is less than 2 ng/ml.